Cancerland

by David Scadden

  In the 1950s and early 1960s, Burkitt and his colleagues traveled thousands of miles to pinpoint the locations of children who developed a type of lymphoma rarely seen elsewhere in the world. (He joked that three doctors visiting hospitals across the continent “enjoyed the safest-ever safari in Africa.”) The common factors in the cases Burkitt studied turned out to be a history of malaria, which weakened the immune system, and infection with the virus that came to be known as the Epstein-Barr. The malaria was spread by a certain type of mosquito, which is common in the region Burkitt studied. The virus, which most commonly causes mononucleosis, is so ubiquitous that 50 percent of all children contract it by age five. After infection, it remains in the body, where it is almost always kept at bay by the immune system. It contributes to cancer only when other factors, like a weakening of the immune system, are present.

  What was eventually called Burkitt’s lymphoma was characterized by extremely fast-growing tumors, typically found first in the lymph nodes of the neck or jaw, leading to a rapidly worsening illness, organ failure, and death. Under the microscope, lymph node biopsies exhibit a distinctive pattern that came to be called the “starry sky.” The “sky” is composed of large, densely packed tumor cells. The “stars” are made of debris left behind by the white blood cells that attempt to fight off the cancer. Although he became famous for his work on this malignancy, Burkitt would go on to do other important work. He helped establish the link between dietary fiber and the prevention of colon cancer and devised methods for producing cheap artificial limbs to help amputees in poor countries. But his most important legacy, in addition to the lives he saved, was his lymphoma research.

  * * *

  Although Burkitt, Isaacs, Lindenmann, and Miller had achieved real milestones, science was far from a true understanding of the causes of most cancers, let alone treatments that could be termed “cures.” Nevertheless, people hungered for answers to the questions that naturally arise in the case of cancer, especially “How did I get it?” and “How do I get rid of it?” Too often, the press, attuned to the power of the topic, seized upon reports published in serious journals and simplified them in ways that surely exasperated physicians. In 1962, Life magazine famously announced, on a cover that also featured a big photo of Marilyn Monroe, “New Evidence That Cancer May Be Infectious.” Life was a staple of doctors’ waiting rooms all across America. (I would bet that issue landed in Dr. Baldino’s office in Wyckoff.) By using the word may, the editors preempted critics who knew that the headline was sensationalistic. This left it to doctors to explain that no, cancer wasn’t contagious in the way people might imagine (as in transmitted person to person) and that patients needn’t be quarantined.

  In addition to alarming patients and the general public, the idea that cancer was infectious spurred a big government investment in research intended to discover more cancer-causing viruses or bacteria. Looking back on this time, it is surprising to see such a focused effort. Scientific progress doesn’t usually follow the kind of straight-line route that can be directed from some central authority. More typically, research in one area gets unexpected aid from a breakthrough in another. Thus, more than a decade would pass, and enthusiasm would wane, before it became possible to see how we might actually create—or engineer—new models of life that would help us study and intervene in the cancer process.

  In 1969, a team at Harvard led by Jonathan Beckwith became the first to isolate a specific gene among the three thousand or so in a type of bacteria called Escherichia coli. Soon came the gene-splicing experiments of biochemist Paul Berg of Stanford, who combined the DNA of two separate types of viruses to create a novel, engineered DNA molecule. (This process was called recombinant DNA methodology.) Berg, who had earned his doctorate at Case, had immersed himself in basic cancer research starting in 1952 and plunged into a lifelong investigation of biology at its most basic levels. He was followed by Fred Sanger, who devised a method for rapidly producing an image of long stretches of DNA. These discoveries and others excited scientists but sent shivers through the ranks of theologians, who wondered if humanity would usurp a role previously played only by God.

  This concern, that scientists would abuse the power of the new biological science, echoed the fears raised when physicists unlocked the atom in the 1940s. Science and technology had reached a point where people could imagine them producing catastrophes that might affect millions of people and, perhaps, humanity itself. The public’s anxiety, which was reflected in science fiction movies and apocalyptic novels like On the Beach, had been appreciated by Beckwith’s group. When their achievement was announced, a member of the team, medical student Lawrence Eron, said, “The only reason the news was released to the press was to emphasize its negative aspects.” Eron hoped that society would engage in a serious conversation about genetic engineering’s potential to shape human populations for ill, as well as for good.

  The discussion got going in earnest in 1974 when a group of biologists, including James Watson, declared they would suspend certain kinds of research out of fear that they would create something dangerous in their labs. (Watson had, along with Crick, received the Nobel Prize in 1962.) In a letter published in the American journal Science, and a British one called Nature, this group said it was concerned that gene splicing could produce drug-resistant microorganisms or cancer-causing viruses. “There is serious concern,” wrote the scientists, “that some of these artificial DNA molecules could prove biologically hazardous.”

  Noting that much of the gene-splicing work being done involved E. coli, which is found inside every human being and throughout our environment, they said that any unwanted creations based on this bacterium could quickly spread. To avoid this possibility, they asked colleagues to suspend aspects of their work too. In addition to Watson, the signers included David Baltimore of MIT and Paul Berg.

  A year later, Berg chaired a landmark meeting at a conference center on the Pacific coast called Asilomar, where migrating monarch butterflies flitted among the Monterey pines. The context for this gathering included the political crisis of the Watergate burglary scandal, which had forced a U.S. president to resign for the first time in history. Combined with the hugely unpopular war in Vietnam, Watergate had left many Americans feeling disillusioned and skeptical of those in authority who held the public trust. Opinion polls showed a steep decline in the public’s trust in all sorts of institutions and authorities. Science and medicine weren’t helped by revelations, in 1972, of a federally funded experiment called the Tuskegee Study, which denied treatment to African American men with syphilis so that the disease could be studied. The fact that government and science had collaborated in the abuse of the men in the study frightened people as they contemplated technologies that had the potential to produce both great benefits and vastly more harm than anything mankind had ever before created. Berg was among them.

  The scientists and physicians at Asilomar were joined by lawyers and journalists, who advised them on everything from liability issues to communications. For some of the scientists, who never considered the issue, the fact that laboratories were also work sites covered under labor, health, and safety laws was a disturbing revelation. Few had ever considered the risks they were courting as they worked on what would be, for all intents and purposes, new forms of life. Others, including Norton Zinder of Rockefeller University, were already concerned that many in this new field—his field—lacked the experience in microbiology to keep themselves, their colleagues, and the public safe. Working first in small groups and then in one large body, the conference attendees eventually established six categories of genetic experiments, which they ranked according to hazard, and indicated how they should be regulated. On one end of the scale were experiments involving organisms that freely exchanged genes in nature and were already quite variable in the existing environment. On the other end were projects that posed such a high risk of creating new pathogens that they shouldn’t be conducted at all.

  Asilomar, as
the gathering came to be known, produced standards that showed that science was listening to public concerns and eager to hold itself accountable. For those engaged in work deemed most dangerous, the group recommended a “high containment” strategy that required air locks for lab entries and filtering of any air leaving the space where experiments would be done. Anyone entering these labs would have to first shower and don protective gear. Upon exiting, they would have to leave these clothes in a secure area and shower a second time. The cost of upgrading labs to meet the standards would be high. Berg’s own facility had just undergone upgrades costing tens of thousands of dollars (big money in the 1960s), and more would be required if he wanted to pursue the kinds of studies he was contemplating.

  For skeptics, the results of Asilomar suggested that scientists were beginning to understand why thoughtful laypeople might be afraid of technologies that enabled the creation of entirely new life-forms. For those in government and politics, the guidelines produced at the conference served as a template for codes that would eventually have the force of law. In fact, as Asilomar ended, the National Institutes of Health embarked on a four-year process intended to turn the guidelines into enforceable regulations.

  The slow pace of this work was supposed to reassure people that it was being done with care and consideration for a wide diversity of opinion. Of course, some were frustrated with the uncertainty caused by the delay. James Watson, who had so publicly signaled his worries about gene splicing, changed his mind. “Specifically, I was a nut,” he said as he retracted his support for the moratorium on certain experiments. “There is no evidence at all that recombinant DNA poses the slightest danger.”

  Watson spoke with the great authority that comes with a Nobel Prize, but his tone—impatient, if not imperious—was a red flag to anyone who viewed the powerful with some skepticism. In the 1970s, both modern progressives and old-fashioned traditionalists could be discovered among the wary, who found something unsettling in the claims of powerful people, be they scientists, political leaders, corporate chiefs, or bureaucrats. No badge of status was enough to reassure some people, especially those who feared that an overconfident, overempowered elite could be dangerous.

  The fear and anxiety many people felt about science and technology came into full focus in 1978 in Harvard University’s home city of Cambridge, Massachusetts, when Mayor Alfred Vellucci convened public hearings to review the public health implications of DNA research. (Cambridge is also home to the Massachusetts Institute of Technology, so the prospect of this work taking place within the city limits was quite real.) Vellucci, a silver-haired man who was born in 1915, had long feuded with the university over mundane matters like parking and rowdy students. He had often appealed to Cambridge voters by bashing the university and, consequently, earned the ridicule of the student-run satirical magazine called the Harvard Lampoon. At one point in this long-running town/gown dispute, after Lampoon editors mocked Italian Americans by claiming the Irish discovered the New World, Vellucci proposed turning the office building where the magazine kept its offices into a public restroom. He also suggested calling the area around the place Yale Square. And he planted a tree in the sidewalk in front of the place to spoil the view from inside. (Over the years, the tree would suffer much abuse, including shorn limbs and poisoning.)

  At the city council hearing, where Vellucci appeared in coat and tie, he asked witnesses from the Harvard faculty to refrain from using “your alphabet,” by which he meant scientific jargon, because “most of the people in this world are laypeople, we don’t understand your alphabet.”

  The very first person to testify, cell biologist Mark Ptashne of Harvard, struggled with the mayor’s request, sprinkling references to “P1 and P2 laboratories” into his argument. (P1 and P2 labs conducted extremely low-risk work.) When he spoke of the gene-splicing work proposed for Cambridge, he said that “unlike other real risks involved in experimentation, the risks in this case are purely hypothetical.” Ptashne, who was thirty-six, appeared in shirtsleeves and wore long hair and sideburns. He didn’t help his case in the minds of skeptics when he noted that “millions of [E. coli] bacteria cells carrying foreign DNA” had already been “constructed” and that “so far as we know, none of these cells containing foreign DNA has proved itself hazardous.”

  Brilliant as he was, Ptashne was no match for the mayor in the political forum of a city council meeting. After the Harvard professor made his statement, Vellucci read off a long list of questions, which he suggested Ptashne write down. (He did.) First the mayor asked for a “100 percent certain guarantee that there is no possible risk” in any experiments envisioned by Harvard scientists. Then he moved on to a series of questions intended to alarm the crowd:

  “Do I have E. coli inside my body right now?”

  “Does everyone in this room have E. coli inside their bodies?”

  “Is it true that in the history of science, mistakes have been known to happen?”

  “Question: Do scientists ever exercise poor judgment?”

  “Do they ever have accidents?”

  “Do you possess enough foresight and wisdom to decide which direction that humankind should take?”

  Before Vellucci was finished, he had warned of monsters created in laboratories and stirred up others on the council, who continued the attack. Council member David Clem complained that “there are already more forms of life in Harvard Square than this country can stand” and then asked Ptashne, “What the hell do you think you are going to do if you do produce” a dangerous organism?

  Ptashne was exasperated by the questions and would later call the proceedings “an unbelievable joke.” But the Cambridge community of scientists was not monolithic. David Nathan, a physician and biologist at Boston Children’s Hospital, encouraged the politicians to complete their work on safeguarding the public because he was raising children in the city of Cambridge and didn’t see any need for unnecessary risk-taking. The mayor and council ultimately banned recombinant DNA work inside the city limits for nearly a year. In this time, they wrote and approved a number of biological safety ordinances and created a review board to consider all planned recombinant DNA research. Among the members of the board were a Catholic nun, engineers, a physician, and a professor of environmental planning.

  Despite the mayor’s inflammatory rhetoric and fears among the faculty that the city might shut down research, something positive grew out of the Cambridge process. The city got ahead of other communities and figured out a way to accommodate science. In a few years, Harvard faculty and commercial research firms would make the city a hub for biotechnology—which would, in turn, become a driver for business growth. In an era when brainpower was quickly replacing heavy industry as a source of economic growth and development, cities, states, and nations that had found a way to regulate science without too much interference had enormous advantages.

  When the new technologies were considered in political forums and at public meetings, nonscientists got a chance to question the experts and learn things that made them feel less wary and worried. Unfortunately, very few Americans lived in communities where scientists conducting recombinant DNA research were invited to answer their questions. The consequences of this gap between public understanding and the facts allowed all sorts of mischief to occur. One of the strangest episodes came a year after the Cambridge hearing, with the publication of a book, labeled nonfiction, that purported to tell the story of an eccentric millionaire who had brought scientists to a private island where they had produced his clone—a little boy—who was happily maturing inside a laboratory enclave.

  In His Image: The Cloning of a Man was written by a journalist named David Rorvik, who had contributed articles to The New York Times and other publications. Rorvik knew enough science to make the tale plausible, and he was an excellent storyteller who provoked all the fears and ethical controversies you might imagine would follow a “credible” report on the first human clone. (He said the boy was fourteen months
old, that he had seen him, and that he was “alive, healthy, and loved.”)

  After he was interviewed by Tom Brokaw on the NBC network’s Today show, where he refused to divulge the name of the man who was cloned, Rorvik’s book flew to the top of bestseller lists across the country. Publishers around the world clamored for the rights to publish translations. With rising sales came rising controversy, including a complaint from a British scientist who objected to his name appearing in the book. A court in London would eventually find in the scientist’s favor and declare the book a hoax. But in the meantime, In His Image created such a stir that a congressional committee conducted a Capitol Hill hearing on the matter.

  David Rorvik declined to testify before Congress, saying he was too busy on his international book tour. However, the experts who did speak to the Subcommittee on Health and the Environment of the House Committee on Interstate and Foreign Commerce explained that since no one had ever produced a clone of any mammal, the idea that a wealthy man had built a secret lab, staffed it with the best scientists, and cloned himself was ludicrous. However, they did speak encouragingly of new technologies and genetic research that could produce important insights into and even treatments for some illnesses, including cancer. This work was also likely to reveal important insights into the aging process. Robert G. McKinnell of the University of Minnesota noted experiments involving repeated transplantation of cells from a developing animal embryo to test theories about aging. (McKinnell would publish widely in cell biology and contribute to a textbook called The Biological Basis of Cancer.)